biostudies-literature00560Wang YNIDDK NIH HHSNIAID NIH HHSNHLBI NIH HHSNCI NIH HHSPHS HHS631-42https://www.ebi.ac.uk/biostudies/studies/S-EPMC3572910biostudies-literatureUnknown11(6)Type I interferon (IFN-I) promotes antiviral CD8(+)T cell responses, but the contribution of different IFN-I sources and signaling pathways are ill defined. While plasmacytoid dendritic cells (pDCs) produce IFN-I upon TLR stimulation, IFN-I is induced in most cells by helicases like MDA5. Using acute and chronic lymphocytic choriomeningitis virus (LCMV) infection models, we determined that pDCs transiently produce IFN-I that minimally impacts CD8(+)T cell responses and viral persistence. Rather, MDA5 is the key sensor that induces IFN-I required for CD8(+)T cell responses. In the absence of MDA5, CD8(+)T cell responses to acute infection rely on CD4(+)T cell help, and loss of both CD4(+)T cells and MDA5 results in CD8(+)T cell exhaustion and persistent infection. Chronic LCMV infection rapidly attenuates IFN-I responses, but early administration of exogenous IFN-I rescues CD8(+)T cells, promoting viral clearance. Thus, effective antiviral CD8(+)T cell responses depend on the timing and magnitude of IFN-I production.Cell host & microbeTiming and magnitude of type I interferon responses by distinct sensors impact CD8 T cell exhaustion and chronic viral infection.PMC35729102T32HL007317-31U01 AI067854T32 DK0072965T32DK007296R01 CA043059T32 HL007317A1067854Gilfillan SCella MSwiecki MColonna MWang YSchreiber RDAlber G56falseTiming and magnitude of type I interferon responses by distinct sensors impact CD8 T cell exhaustion and chronic viral infection.Type I interferon (IFN-I) promotes antiviral CD8(+)T cell responses, but the contribution of different IFN-I sources and signaling pathways are ill defined. While plasmacytoid dendritic cells (pDCs) produce IFN-I upon TLR stimulation, IFN-I is induced in most cells by helicases like MDA5. Using acute and chronic lymphocytic choriomeningitis virus (LCMV) infection models, we determined that pDCs transiently produce IFN-I that minimally impacts CD8(+)T cell responses and viral persistence. Rather, MDA5 is the key sensor that induces IFN-I required for CD8(+)T cell responses. In the absence of MDA5, CD8(+)T cell responses to acute infection rely on CD4(+)T cell help, and loss of both CD4(+)T cells and MDA5 results in CD8(+)T cell exhaustion and persistent infection. Chronic LCMV infection rapidly attenuates IFN-I responses, but early administration of exogenous IFN-I rescues CD8(+)T cells, promoting viral clearance. Thus, effective antiviral CD8(+)T cell responses depend on the timing and magnitude of IFN-I production.2012-01-01T00:00:00Z2012 Jun2020-10-29T13:05:19Z2019-03-27T01:04:50ZS-EPMC35729102270462310.1016/j.chom.2012.05.003